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Review
. 2016 Jun;74(6):374-86.
doi: 10.1093/nutrit/nuw008. Epub 2016 May 3.

Early-life enteric infections: relation between chronic systemic inflammation and poor cognition in children

Reinaldo B Oriá  1 , Laura E Murray-Kolb  2 , Rebecca J Scharf  2 , Laura L Pendergast  2 , Dennis R Lang  2 , Glynis L Kolling  2 , Richard L Guerrant  2
Affiliations
Review

Early-life enteric infections: relation between chronic systemic inflammation and poor cognition in children

Reinaldo B Oriá et al. Nutr Rev. 2016 Jun.

Abstract

The intestinal microbiota undergoes active remodeling in the first 6 to 18 months of life, during which time the characteristics of the adult microbiota are developed. This process is strongly influenced by the early diet and enteric pathogens. Enteric infections and malnutrition early in life may favor microbiota dysbiosis and small intestinal bacterial overgrowth, resulting in intestinal barrier dysfunction and translocation of intestinal bacterial products, ultimately leading to low-grade, chronic, subclinical systemic inflammation. The leaky gut-derived low-grade systemic inflammation may have profound consequences on the gut-liver-brain axis, compromising normal growth, metabolism, and cognitive development. This review examines recent data suggesting that early-life enteric infections that lead to intestinal barrier disruption may shift the intestinal microbiota toward chronic systemic inflammation and subsequent impaired cognitive development.

Keywords: cognition; enteric infections; environmental enteropathy; intestinal microbiome; malnutrition.

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Figures

Figure 1
Figure 1
Proposed model of how a prolonged state of enteric infection/malnutrition causes systemic inflammation, thereby affecting the gut–brain axis. Malnutrition and repeated enteric infection in the first 2 years of life may cause intestinal barrier leakage. Intestinal dysbiosis may facilitate luminal-to-blood pathogenic bacterial translocation and, consequently, low-grade systemic inflammation. Circulating bacterial products may activate the endothelial cells, which form the blood–brain barrier, to release proinflammatory cytokines to prime and activate microglial cells. An early-in-life subclinical neuroinflammatory state may affect cognitive development in children. Abbreviations and symbols: ↑, increased; ↓, decreased; BBB, blood–brain barrier; CBPs, circulating blood products; IL, interleukin; MHC, major histocompatibility complex; TNF-α, tumor necrosis factor-α.
Figure 2
Figure 2
Dynamic interactions between diet, intestinal microbiota, brain, and liver.
See this image and copyright information in PMC

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